tbuckley/cabot-search huggingface dataset:
An immunogenomic signature for molecular classification in melanoma.
Authors: Yang Liu, Qian Wang, Shanshan Xiao, Tao Wang
Journal: Journal of Clinical Oncology (2023)

e21562 Background: Melanoma is one of the most aggressive tumors in the world, characterized by an increasing incidence and high mortality with half of the patients dying from the advanced tumors. The melanoma tumor is very heterogenous and the appropriate classification of subtypes is the key to guide precision treatment. Previous studies have revealed the important roles of immune cells in melanoma. Therefore, the better classification method and comprehensive analysis of immune cells and immune-related genes can help to better understand the tumor progression and develop effective treatment strategies in melanoma. Methods: Two datasets containing RNA sequencing data and paired patient information with melanoma were collected in this study. The first dataset of skin cutaneous melanoma patients downloaded from The Cancer Genome Atlas database (n = 204) was used as the training set, and the second dataset from a published study was used as internal validation set (n = 102). Single sample gene enrichment analysis (ssGSEA), ESTIMATE, CIBERSORT and k-means analysis were used to classify melanoma patients into two different immune clusters. We then constructed a molecular signature with nine immune related genes that could predict the overall survival (OS) of melanoma patients by LASSO regression and Cox regression analysis. The accuracy of the risk signature was then verified in eight independent cancer types. Results: The melanoma patients were divided into two different immune clusters, the high-immune cell infiltration cluster (Immunity_H) and low-immune cell infiltration cluster (Immunity_L). 1,556 and 1445 differentially expressed genes (DEGs) between the Immunity_H and Immunity_L were detected in the training set and validation set, respectively. Accordingly, 677 and 147 genes associated with overall survival (OS) was further selected by Univariate Cox regression analysis. 59 genes were shared between the 677 and 147 OS related genes. Eventually, 9 DEGs (CST7, CSF2RB, SPARC, SPOCK2, PLA2G2D, MYO1G, NCF1, ICOS and HSH2D) were screened out by LASSO regression analysis and were then subjected to multivariate Cox regression analysis to further construct the prognostic signature. Patients were divided into high-risk and low-risk groups based on the computed risk threshold. Kaplan-Meier analysis indicated that patients in the high-risk group had a significantly worse OS. Finally, 8 independent external pan-cancer cohorts were used to validate the robustness of the model. Conclusions: This study identified two immune-related clusters and a risk signature based on nine immune-related genes was constructed, which could predict the melanoma cancer OS and the constructed model can be used as prognosis predictor in melanoma.
Long-term clinical and psychosocial outcomes of surveillance in Li Fraumeni syndrome.
Authors: Milita Zaheed, Christine E Napier, Elisa J Cops, Nick Ferris, Kate Moodie, Brad Milner, Daniel Moses, Nicola Poplawski, Eryn Gaye Dow, Marion Harris, Kathy Tucker, Alison Trainer, Paul James, David Morgan Thomas, Mandy L. Ballinger
Journal: Journal of Clinical Oncology (2023)

10578 Background: Li Fraumeni Syndrome (LFS) is a high penetrance multi-organ cancer predisposition syndrome, associated with a significant lifetime risk of developing cancer. The Surveillance study in Multi-Organ Cancer prone syndromes (SMOC+) is investigating the utility of annual surveillance, with inclusion of whole-body magnetic resonance imaging (WBMRI), for hereditary cancer syndromes without well-established risk management strategies. Here we report the long-term clinical and psychosocial outcome of surveillance in participants with LFS. Methods: Multimodality surveillance in this multi-centre, prospective, longitudinal, observational study for adult participants with LFS included annual clinic review and examination, WBMRI, breast MRI (MRIB), full blood count, prostate specific antigen; 2-5 yearly gastro-intestinal endoscopy and faecal occult blood test in intervening years. Quantitative psychometric evaluations were requested at regular intervals each year using Hospital Anxiety and Depression Scale (HADS), the Impact of Events scale anchored to cancer (IES-C), and the Impact of Events scale MRI (IES-MRI). Results: From July 2013 to December 2021, 132 (67% female) participants were enrolled at a median age of 36 (range 18-69 )years. There were 116 prior diagnoses of neoplasms among 68 (52%) participants, including 27 (20%) with multiple primaries. At a median follow up of 4 years, 46 new primary malignancies were diagnosed in 30 (23%) individuals, with median age at diagnosis of 43 (range 24-71 years). Four (3%) individuals developed recurrence of a prior malignancy. The malignancies were detected as a result of WBMRI (27), MRIB (7), gastroscopy (1), colonoscopy (1) and clinical review and examination (17). The most frequent new primaries were leiomyosarcoma and breast cancer (Table). Overall, 22 (17%) are not currently participating due to cancer related death (10), active cancer (6) or other life events (6). At 4 years after enrollment, 94, 80 and 50 participants completed at least one HADS (463 unique observations), IES-C (362 unique observations), and IES-MRI (268 unique observations) questionnaire, respectively. Controlling for demographic and cancer history variables, there was no evidence of changes in overall anxiety or depression (p=0.2), nor in degrees of distress associated with cancer (p=0.06) or WBMRI (p=0.6) over time. Conclusions: In LFS, annual surveillance with WBMRI is feasible and well tolerated, with no difference in distress experienced in the longer term. Over 80% of participants continue to engage with surveillance. The majority of cancer-affected individuals were able to resume surveillance after management of early disease. [Table: see text]
Real-world experience with liposomal doxorubicin in metastatic and locally advanced sarcoma.
Authors: Allen Hodge, John A. Charlson
Journal: Journal of Clinical Oncology (2023)

e18795 Background: Sarcomas are a type of cancer that have been historically difficult to treat given their rarity, numerous subtypes, and variable response to treatment. Doxorubicin is the most used first-line chemotherapy in metastatic sarcoma; pegylated liposomal doxorubicin (PLD) has been explored as a potentially better tolerated alternative to free doxorubicin, with less myelosuppression, alopecia, and potentially less cardiotoxicity. In this work, we examine the efficacy and real-world challenges of using PLD as treatment for metastatic and locally advanced sarcoma. Methods: Medical records of metastatic and locally advanced sarcoma patients treated with single agent PDL as a therapy were obtained from a single tertiary medical center. Retrospective analysis was conducted to measure overall survival, progression free survival, best overall RECIST response, dosage, and complications. Results: 58 subjects were identified with 52% being male and 48% female. Sarcoma subtypes included liposarcoma (28%), leiomyosarcoma (21%), undifferentiated sarcoma (16%), synovial sarcoma (5%), and other subtypes (30%). Mean age at time of initiating therapy was 64 years. 22% of patients had previously been treated with doxorubicin, in the neo-adjuvant or adjuvant setting. Patients received an average of 5 cycles of PLD. Starting dosage was 50 mg/m² every 28 days, however, changes to lower the starting dose were made in 38% of cases to adjust for anticipated tolerance, and in 21% subsequently due to side effects such as cutaneous toxicity and fatigue. There were no complete responses, 12% partial response, 31% stable disease, and 57% progressive disease. Mean overall survival and progression free survival was 452 and 180 days, respectively. Sixty-seven percent of participants had at least one follow-up echocardiogram, and 15% of those had some evidence of cardiotoxicity, with an ejection fraction of &lt; 50% or 10% decrease from baseline. Of the participants with changes in ejection fraction, 67% had received prior anthracycline therapy and 33% had received a total lifetime dose of doxorubicin exceeding the recommended 500 mg/m² limit. Conclusions: PLD is an option for first-line therapy for metastatic sarcoma in general, however, its efficacy remains limited in a real-world setting with most patients showing a best RECIST response of progressive disease and a mean progression free survival of 180 days. While PLD is generally well-tolerated, there are potential toxicities that require attention, including cutaneous toxicity, such as hand-foot syndrome, and infusion reactions. Furthermore, a significant portion of our sample had echocardiographic changes, with decreased ejection fraction, pointing out that, while PLD may be less cardiotoxic than free doxorubicin, there is potential risk. This highlights the need to continue the search for novel therapeutic strategies in metastatic and locally advanced sarcoma.
OMNIA-1: A phase I/II study, an IL-2R-βγ targeted antibody-IL-2 fusion protein, as monotherapy or in combination with anti-PD-1 or anti-CTLA-4 antibodies, in patients with advanced melanoma.
Authors: Paolo Antonio Ascierto, Guillermo de Velasco, Thomas Eigentler, Nicolas Isambert, Julie Mouton, Caroline Robert, Claudia Michaela Schusterbauer, Jayanthi Vijayakumar
Journal: Journal of Clinical Oncology (2023)

TPS9599 Background: ANV419 is a potent and selective IL-2Rβγ targeted antibody IL-2 fusion protein, designed to enable the delivery of high dose interleukin-2 (IL-2) to patients in order to stimulate anti-tumour response and minimise toxicities. Recombinant IL-2 (proleukin) induces durable responses in approximately 10% of patients with melanoma. Signalling through IL-2Rα expressing cells is believed to limit its therapeutic potential in cancer. By eliminating binding to IL-2Rα, ANV419 could lead to increased anti-tumor effect while increasing tolerability. The ANV419-001 first-in-human study (NCT 04855929) demonstrated that ANV419 preferentially stimulates cytotoxic CD8+ T and natural killer (NK) cells over immunosuppressive regulatory T cells, with a significantly longer half-life than that of conventional IL-2. The safety and tolerability data from this study confirmed that ANV419 delivers high molar equivalents of IL-2 in a tolerable and convenient way. Methods: ANV419 is being evaluated in a global multicentre, open-label, randomized Phase I/II study in patients with unresectable or metastatic cutaneous melanoma to assess the safety and efficacy of intravenous ANV419 as monotherapy and in combination with anti-PD1 or anti-CTLA-4 antibodies. The OMNIA-1 study leads in with a monotherapy dose expansion part, followed by a combination dose-finding with either anti-PD-1 or anti-CTLA-4 and a combination dose expansion part. ANV419 is administered intravenously every 2 weeks as monotherapy and every 3 weeks when given in combination. Patients with advanced cutaneous melanoma, no active brain metastases and whose disease has progressed on or following at least 1 line of standard of care immunotherapy are eligible. In Part 1, a total of 30 patients will be randomised and evaluated for response to Q2W ANV419 monotherapy (108 µg/kg or 243 µg/kg). In Part 2, escalating doses of Q3W ANV419 are evaluated to define the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) in combination with pembrolizumab (200 mg) or ipilimumab (3 mg/kg). In Part 3, the efficacy and safety of ANV419 in combination with the approved doses pembrolizumab or ipilimumab will be evaluated using a Simon’s 2-stage design. Up to 130 patients are planned to be enrolled. Patients will be stratified according to BRAF mutation status. AEs are assessed according to CTCAE V5.0. Tumour response is determined using RECIST 1.1 criteria. The study is conducted at sites in the US, France, Spain, Germany, Italy, and UK. The first patient was dosed in December 2022. Preliminary monotherapy efficacy data are expected by Q1/2024. Clinical trial information: NCT05578872 .
Therapeutic evaluation on Chinese calycosin decoction for chemoradiotherapy induced thrombocytopenia.
Authors: Guangmei Lv, Meng Hu, Haijun Wan Wan, Wei Liang, Wentao Ha, Sunyan Zhao, Yongling Gong
Journal: Journal of Clinical Oncology (2023)

e24153 Background: Chemotherapeutic thrombocytopenia is often accompanied with hospitalized cancer patients associated with anti-tumor therapy, so called CRIT (Chemoradiotherapy induced thrombocytopenia). In addition to the risk of thrombocytopenic hemorrhage, we also observed the implementation of the originally scheduled chemoradiotherapy with limits of dose and frequency. However, CRIT therapy administered with Chinese calycosin decoction may benefit those affected patients. Methods: Forty CRIT patients diagnosed in the Nanjing 1st Hospital,China, from 2019 to 2021, were enrolled and divided randomly into herbal group (n = 19) and control group (n = 21). Herbal group was treated with additional calycosin decoction, while control group received conventional treatment related to CRIT in the mean time. The primary endpoint of efficacy assessment was time to recovery (TTR) for CRIT. Secondary endpoints were delayed termination rate (DTR) of chemoradiotherapy, incidence of hospitalization (IH) and incidence of platelet transfusion (IPT). Results: The effective rate of herbal group (13/19, 68.4%) and control group (12/21, 57.1%), and no grade 3 or 4 adverse gastrointestinal reactions were observed during treatment. Compared with the control group, TTR of grade Ⅰ-Ⅲ CRIT patients in herbal treatment group was relatively shorter (11.1±1.8d vs 13.8±2.1d), DTR (3/15,20% vs 7/16, 44%), and IH (7/15,47% vs 11/16,69%) was significantly lower, difference was statistically significant (P &lt; 0.01). TTR, DTR, IH and IPT of grade Ⅳ CRIT patients were not significantly different between the two groups (P &gt; 0.05). Conclusions: Chinese herbal managing of CRIT with calycosin decoction might be an additional choose option, help to benefit stand dosage implementation of chemoradiotherapy and socioeconomic cost.
Multicenter analysis of melanoma recurrence pattern and management after adjuvant immunotherapy.
Authors: Sergio Martínez Recio, Maria Alejandra Molina, Eva Muñoz-Couselo, Alberto Rafael Sevillano Tripero, Juan Martin-Liberal, Mayra Orrillo, Luis Antonio Fernandez, Maria Quindós Varela, Rocio Lesta, Andrés Barba, Ivana Sullivan, Margarita Majem
Journal: Journal of Clinical Oncology (2023)

e21573 Background: PD-1 inhibitors improve outcomes in resected stage II-IV melanoma. However, recurrence patterns and prognostic factors are less known. Methods: We conducted a retrospective study in resected stage II-IV melanoma patients (p) treated with adjuvant PD-1 inhibitors (clinical practice or clinical trials) from 5 centers. Demographic, disease characteristics, adjuvant therapy, recurrence, treatment at relapse and outcome were recorded. Descriptive assessment for recurrence patterns and analysis for prognostic factors were performed. Results: From June 2017 to June 2022, 181 p were included. Median age was 59 years [22-81], 57% were male, 85% had cutaneous melanoma, 28% had BRAF V600E mutation. 9 p (5%) presented stage II, 147 (81%) stage III and 25 (14%) stage IV. Ulceration was present in 59% p, mitotic rate &gt;1/mm 2 in 84%, Breslow index &gt;3 mm in 65% and elevated LDH in 51%. 81% p received PD-1 inhibitors alone and 19% in combination with other immunotherapies. 52% of p completed treatment, 12% discontinued due to toxicity and 26% due to relapse. 13% of p presented grade 3-4 adverse events and there was a grade 5 myocarditis. With a median follow-up of 18,1 months, 68 (37%) p recurred (Table). Median relapse free survival (RFS) was 48,8 months (95% CI 31,1-66,4). Recurrence was significantly associated with a higher stage, mitotic rate, LDH level and Breslow index, BRAF V600E mutation, non-cutaneous melanoma and delayed initiation of adjuvant immunotherapy in univariate analysis (p&lt;0,05). Stage, non-cutaneous melanoma and initiation of immunotherapy &gt;3 months (16% p) were associated with higher recurrence in multivariate analysis (&lt;0,05). Locoregional recurrence was treated in 23 p with surgery (14p), surgery + RT (7p) or RT alone (2). Systemic recurrence was treated in 50 p: all BRAF mutant p received targeted therapy (24p, 43%) with a disease control rate (DCR) of 91% and a median progression free survival (PFS) of 56 months (95% CI 24,1-NR); BRAF wild type p (26p, 47%) were treated with anti-PD-1 alone (9p) or in combination (7p), anti-CTLA-4 (2p), chemotherapy (1p) or best supportive care (7p), with DCR of 33% and a median PFS of 8 months (95% CI 6,9-10,8). Conclusions: We observed a 37% relapse rate and systemic recurrence were more frequent than locoregional recurrence. Treatment at relapse with targeted therapy in BRAF mutant p achieved higher DCR and PFS than immunotherapy in BRAF wild type p; with better outcomes than previously reported.[Table: see text]
A whole-food, plant-based dietary intervention and cognitive function in women with metastatic breast cancer.
Authors: Jeremy McGuire, Thomas Campbell, Nikesha Gilmore, Eva Culakova, Lindsey Jean Mattick, Michelle Christine Janelsins, Luke Joseph Peppone, Erin Campbell
Journal: Journal of Clinical Oncology (2023)

e24160 Background: Disease-specific quality of life (QOL) is consistently regarded as one of the most important outcomes by women with metastatic breast cancer (mBC), and it predicts survival. Treatment-related symptoms such as cognitive impairment greatly impact QOL in women with mBC. Patients undergoing treatment for breast cancer are highly interested in diet and nutrition, but despite this high level of interest, very few trials have tested dietary interventions in women receiving systemic breast cancer therapy and; the majority of research has been conducted in survivors who have completed primary treatment. Given the limited treatment options for cognitive impairment we evaluated whether our results show a whole food plant based (WFPB) dietary intervention might improve perceived cognitive function (CF) in women undergoing treatment for metastatic breast cancer. Methods: Patients with stage 4 breast cancer receiving treatment were randomized 2:1 into 2 arms: 1) WFPB diet (n = 20) or 2) usual care (n = 10) for 8 weeks with assessments at baseline, and 8 weeks. Our WFPB diet consisted of an ad libitum whole-food, plant-based diet; 3 meals/day were provided, which included fruits, vegetables, whole grains, nuts/seeds and excluded meat, dairy, eggs, added oils, solid fats and most sugars. Patient reported outcomes for perceived CF were collected using FACT- COG and EORTC-QLQ-C30. Paired t-tests were used to assess within group changes from baseline to week 8. The between group difference (WFPB diet vs control) was assessed by ANCOVA model. Results: Patients on the WFPB diet began with a mean baseline score of 140.8 on the FACT-COG which significantly improved to 156.6 (p = 0.005) at 8-weeks post intervention. The reported minimally important difference (MID) between groups is (9.6) and we observed a clinically significant difference of 17.1 (p = 0.03). Similar results in CF were observed for EORTC-QLQ-C30. The baseline mean score of 73.3 was improved to 84.7 (p = 0.004) at 8-weeks post intervention. The reported MID between groups is (4) and we observed a clinically significant difference of 12.6 (p = 0.07), with no significant changes in perceived CF for the control group. Conclusions: Our 8-week WFPB diet resulted in clinically meaningful and statistically significant improvements in perceived cognitive function in women with metastatic breast cancer. A phase 3 clinical trial is needed to confirm the results of this novel intervention. Funding: 3UG1CA189961. Clinical trial information: NCT03045289 .[Table: see text]
The combination therapy of anlotinib and penpulimab for the treatment of small cell lung cancer after platinum-based chemotherapy: Results of a phase II exploratory study.
Authors: Nong Yang, Yongchang Zhang, Liang Zeng, Haiyan Yang, Chunhua Zhou, Li Liu, Yi Xiong, Wenjuan Jiang, Zhan Wang, Fanxu Zeng, Qun Chen, Yuanqing Feng, Chengzhi Zhou, Zhijun Wu, Bing Zhang, Xiantao Li, Maoliang Xiao, Cunji Wang
Journal: Journal of Clinical Oncology (2023)

e20628 Background: Anlotinib is a multi-target receptor tyrosine kinase inhibitor that has been developed in China. It works by inhibiting various kinases involved in angiogenesis and tumor cell proliferation, including VEGFR, FGFR, PDGFR, and c-Kit. The results of the Phase II ALTER1202 trial showed that patients who received anlotinib as a third-line or later treatment after failing at least two chemotherapy regimens had a better progression-free survival (PFS) and overall survival (OS) compared to those who received placebo. In light of these results, the combination of anlotinib and penpulimab (a novel PD-1 inhibitor) is being studied as a second-line treatment for small cell lung cancer patients who failed first-line chemotherapy with platinum-containing drugs. Methods: This open-label, single-arm, multi-center, Phase II exploratory study (NCT050019710) enrolled patients with small cell lung cancer who had previously received platinum-based chemotherapy. Participants were given 200mg of penpulimab every three weeks and 10mg of anlotinib daily, with a two-week on and one-week off schedule, until disease progression, unacceptable toxicity, or study discontinuation. The primary objective of the study was to evaluate the antitumor activity of the combination therapy using the objective response rate (ORR) as measured by RECIST v1.1. Secondary objectives included evaluating the disease control rate (DCR), PFS, OS, and the safety and tolerability of the combination therapy. Results: As of January 31, 2023, 21 patients (median age 58 years, with 66% having ECOG performance status of 0 or 1, 95% being male) had been enrolled and received treatment. Of these, 18 patients were evaluable for RECIST and had an ORR of 33.33% (6/18) and a DCR of 77.78% (14/18). The median PFS was 5.934 months with a 6-month PFS rate of 33.33%. The median duration of response was 8 months. Nineteen of the 21 patients (90%) experienced treatment-related adverse events, with 4 patients (21%) experiencing grade 3 or higher adverse events. The most common adverse events related to anlotinib were hepatic injury, hematotoxicity, and hypertension. Conclusions: The combination of penpulimab and anlotinib showed promising clinical benefits and a favorable safety profile in small cell lung cancer patients who failed first-line platinum-based chemotherapy. Clinical trial information: NCT05001971 .